The scarcity of human embryonic tissue and the difficulty in manipulating this tissue for research purposes has increased the use of human induced pluripotent stem (iPS) cells and their in vitro differentiation systems. While factors that influence cell development and maturation have been explored, it is difficult to recapitulate embryonic development in vitro. The cell types, cellular niches/structures, and the resulting embryonic patterning are influenced by the artificial conditions in the in vitro setting, which often leads to disorganized, semi-complete development of organ systems.
Current published in vitro protocols demonstrate very limited efficiency in differentiating ES and iPS cells to hematopoietic lineages and, in particular, generating significant numbers of primitive hematopoietic stem cells, hematopoietic progenitors, and hematopoietic cells. This may be attributed partly to the inability of in vitro systems to mimic the processes of embryonic development towards the precursor cells of the hematopoietic system. Additionally, in vitro systems experience unwanted differentiation of ES and iPS cells towards non-blood lineages, such as neuroectoderm and cardiac (anterior lateral plate) mesoderm.
As a consequence, current published in vitro protocols produce insufficient numbers of immature hematopoietic output cells to perform hematopoietic stem cell (HSC) and progenitor or mature cell transplants in patients. It also is difficult to produce enough hematopoietic stem cells, hematopoietic progenitor cells, and hematopoietic cells for research and laboratory use.
The ability to generate hematopoietic stem cells, hematopoietic progenitor cells, and mature blood cells from patient derived induced pluripotent stem (iPS) cells, would enable the generation of an unlimited supply of human leukocyte antigen (HLA)-matched transplantable cells (with or without genetic modification, such as to correct a monogenic disease); these transplantable cells would be used for the treatment of both hematological disorders or malignancies where hematopoietic cell transplantation is required. There is a need for compositions and methods that produce such cells.